Plain English Summary

Background and study aims Non-celiac gluten sensitivity (NCGS) is a condition with symptoms similar to that of celiac disease. These include depression, abdominal pain, bloating, diarrhoea, constipation, fatigue, joint pain and a foggy mind. However, despite the number of symptoms common to both conditions, people with NCGS do not test positive for celiac disease or a wheat allergy. Indeed, there is a debate on whether the disease exists at all. The aim of this study is to test the effect of low amounts (doses) of gluten in patients suspected of having NCGS.

Who can participate? Adult patients with persistent NCGS symptoms and having eaten a diet containing gluten for at least the last two months.

What does the study involve? Participants are randomly assigned to one of two groups. Those in group 1 are given a pill containing 4.375 grams of gluten for a week. Those in group 2 are given a dummy (placebo) pill made out of rice starch. Then, after a one week wash-out period (where no treatment is given to either group), the groups cross over with Group 1 taking the placebo and group 2 taking the gluten containing pill for a week. The effects of taking the gluten compared with the placebo are then analysed.

What are the possible benefits and risks of participating? There are no risks associated with taking part in the trial as participants are not taking drugs but common components of a normal diet. Benefits associated with taking part in our trial might be the diagnosis of true NCGS.

Where is the study run from? St. Matteo Hospital (Italy)

When is the study starting and how long is it expected to run for? October 2012 to January 2014

Study design

Primary study design

Secondary study design

Trial setting

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Nonceliac gluten sensivity

Intervention

Patients will be asked to fill in a daily questionnaire in order to assess a rating scale of both intestinal and extraintestinal symptoms over a 5-week period. Participants will be asked to follow a strict gluten-free diet (GFD) starting one week before the randomization and continuing until the end of the study period. After the first week of GFD, patients will be given either gastrosoluble capsules containing purified wheat gluten (10 capsules ingested in no more than two times over the day, corresponding to a daily gluten intake of 4.375 grams, equivalent to about 2 slices of white bread) or gastrosoluble capsules containing rice starch (10 capsules ingested in no more than two times over the day, corresponding to a daily rice starch intake of 4.375 grams) as placebo for one week. At the end of the first treatment week, patients from both arms will continue only their wash-out from gluten, without taking a capsule. Subsequently, individuals belonging to the first arm will be given placebo capsules, while individuals belonging to the second arm will be given gluten capsules. After the second treatment week, all patients will continue with their wash-out from dietary gluten. During the trial, patients will undergo five outpatient weekly appointments, during which patients will provide their filled questionnaires and investigators will count any unused capsules remaining in capsule dispensers.

Secondary outcome measures

Secondary outcomes are:1. The change in individual symptom scores between the 1-week treatment with gluten and the 1-week treatment with placebo2. The identification of patients with true NCGS3. To verify whether laboratory parameters at baseline are predictive of true NCGS. True NCGS patients are defined as having at the end of the trial a delta overall score - calculated by subtracting the weekly overall score under placebo from the weekly overall score under gluten- higher than the mean delta overall score plus two standard deviations. Laboratory predictors include serum IgG AGA, fecal calprotectin, HLA genotyping and intraepithelial lymphocyte density.

Overall trial start date

20/10/2012

Overall trial end date

31/01/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. Adult patients referred to our outpatients' clinics because of persistence of relevant intestinal and extraintestinal symptoms believed by them to be caused by the ingestion of food containing even low doses of gluten.2. Under gluten-containing diet at the time of screening since at least two months3. Happy to undergo ad hoc screening, including: 3.a. Serum determination of IgA anti-transglutaminase and anti-endomysial antibodies3.b. IgG anti-gliadin antibodies (AGA)3.c. Total IgA and IgE3.d. Wheat-specific IgE3.e. Upper endoscopy with collection of multiple duodenal biopsies3.f. HLA genotyping3.g. Fecal calprotectin3.h. Lactose breath test

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Al least 58 randomized participants

Participant exclusion criteria

1. Other significant gastrointestinal diseases, such as inflammatory bowel disease or cirrhosis, 2. Other clinically significant comorbidities such as diabetes, use of nonsteroidal anti-inflammatory agents or systemic immunomodulators3. Pregnancy4. Inability to give written informed consent5. Reported psychiatric disorder 6. Excessive alcohol intakeOnly patients, who at the end of the screening are found not to be affected by celiac disease, wheat allergy, lactose or FODMAP intolerance, Helicobacter pylori infection, giardiasis, and who complain of relevant gluten-dependent symptoms that is affecting the overall quality of life, will be randomized according to a computer-generated list of random numbers held by an independent observer to either the gluten or the placebo treatment group.